Exocrine Pancreatic Function in Pediatric Patients After Two Years of Triple CFTR Modulator Therapy: Is It Possible to Restore Pancreatic Function?

Abstract

Background: Improvement in exocrine pancreatic function in people with Cystic fibrosis (PwCF) after ivacaftor and lumacaftor/ivacaftor has been documented. Data on triple therapy with elexacaftor/tezacaftor/ivacaftor (ETI) are limited. Methods: In this multicenter, prospective, observational study, we reviewed changes in fecal elastase-1 (FE-1) in the pediatric population with exocrine pancreatic insufficiency (EPI) after 2 years of ETI. Patients were classified according to FE-1: mild-moderate EPI as 100-199 mu g/g and severe EPI as <100 mu g/g. Demographic, clinical, anthropometric, and body composition data were collected. Body composition was measured using bioelectrical impedance analysis. Results: Fifty-three children were recruited (58.5% males). The median age was 12 years [IQR: 9.0-14.5], and 56.6% were homozygous for F508del. Values of FE-1 below fifteen were designated with a 0. At baseline, the median FE-1 was 0.00 [IQR: 0.00-0.00]. We observed a slight yet statistically significant improvement in FE-1 values 2 years after ETI (Wilcoxon test, p < 0.05). We classified patients into three groups based on FE-1 values. At baseline, 98% were in the severe EPI group (FE-1 < 100 mu g/g), the remaining 2% were in the mild-moderate group (FE-1 100-199 mu g/g). Two years after triple therapy, six (11.4%) children showed a change in FE-1 to at least 100 mu g/g from the baseline. Three (5.7%) had a change in FE-1 >= 200 mu g/g from baseline, and the other three (5.7%) had a change in FE-1 between 100 and 199 mu g/g. A significant reduction in daily lipase intake was observed (6346 vs. 5703 L/kg/day; p < 0.05). BMI Z-score improved over 2 years (-0.55 vs. -0.38; p < 0.05). Body composition data were available for 27 patients, showing increased fat mass and fat-free mass after ETI therapy. No differences in body composition were found when stratified by EPI groups. Conclusion CFTR modulators have improved pulmonary function and anthropometric measures in PwCF. Based on these findings, CFTR modulators may also enhance exocrine pancreatic function in pediatric patients.